fbpx

molecules of the month

BMS-986158

oral BET inhibitor

4.5 mg QD, phase I/II for cancer

from bromodomain-focused HTS, SBDD

Journal of Medicinal Chemistry

Bristol Myers Squibb

BMS-986158
1 min read

The BMS BET inhibitor, BMS-986158, is in a Ph. I/IIa trial in advanced cancers. During the optimization of the molecule from a carbazole hit, the authors employed a bold scaffold-hopping strategy involving changing the direction of the carbazole core in order to better access a hydrophobic region of the target. The proposed new binding mode was confirmed by X-ray co-crystallography. The molecule’s triazole ring also interestingly binds in a manner in which both unsubstituted N atoms appear to be engaged as hydrogen bond acceptors to different hydrogen bond donors in the protein (Asn140 for one, a water-mediated H-bond to Tyr97 for the other).


request a trial

Drug Hunter is commited to helping industry innovators make informed decisions. Premium members have access to our library of the latest stories in science, written by scientists.

Request a trial to access insights powering the pros in our industry.


already a member? log in: